Regulation of Store Operated Calcium Channels by μ‐opioid Receptor Activation in Mammalian Intracardiac Neurons

Store‐operated calcium channels (SOC) have been implicated in the regulation of intracardiac neuron excitability. The relationship between μ‐opioid receptor activation and SOC activity was examined in cultured intracardiac neurons from neonatal rats using fura‐2 Ca 2+ fluorometry and whole‐cell patch clamp electrophysiology. Activation of μ‐opioid receptors using Met‐enkephalin (ME) and endomorphin‐1 (EM‐1) reversibly depressed both intracellular Ca 2+ elevations and whole‐cell membrane currents mediated by SOC. Preincubation of the neurons in pertussin toxin (PTX) inhibited μ‐opioid receptor modulation of SOC such that SOC‐mediated capacitative Ca 2+ influx was no longer blocked by application of EM‐1. The effects of μ‐opioid receptor regulation of SOC activity were mimicked by bath application of both arachidonic acid (AA) and linoleic acid (LA). Both SOC‐mediated Ca 2+ elevations and whole‐cell membrane currents were inhibited by these fatty acids. However, the AA metabolites, prostaglandin D 2 and prostaglandin E 2 , did not appreciably alter SOC activity. Together, our data suggest that μ‐opioid receptors couple to SOC via a PTX‐sensitive G protein and AA pathway in rat intracardiac neurons.